Effects of drug binding on the esterase-like activity of human serum albumin. V. Reactive site towards substituted aspirins.

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Abstract
To distinguish the reactive site on human serum albumin (HSA) towards aspirin derivatives from that towards p-nitrophenyl acetate (NPA), the effect of the acetylation of HSA by aspirin and the effect of several drugs on the reaction rates of substituted aspirins and NPA with HSA were investigated in pH 7.4 phosphate buffer at 25.degree. C. The substituted aspirins examined were 5-nitroaspirin and 3,5-dinitroaspirin. The acetylation by aspirin affected the reaction rate with 5-nitroaspirin but not that with NPA. The inhibition patterns of the reactions with the aspirins caused by clofibric acid, flufenamic acid and phenylbutazone were different from those with NPA. The complex formation between 5-nitroaspirin and the reactive site of HSA decreased the fluorescence intensity due to the only tryptophan residue (Trp-214) of HSA. Evidently the reactive site towards the aspirins (near Trp-214) is different from that towards NPA which was found previously to be near Tyr-411. From the pH profiles of the kinetic parameters for the reaction of 5-nitroaspirin with HSA, the pKa value of the catalytic group constituting the reactive site towards the aspirins was estimated as .apprx. 9.5.